OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Fostamatinib	901119-35-5	C23-H26-F-N6-O9-P

ANNOTATED BIBLIOGRAPHY

References updated: 20 October 2018

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Review of hepatotoxicity published in 1999 before the availability of protein kinase inhibitors such as fostamatinib).
• DeLeve LD. Erlotinib. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 556.

  (Review of hepatotoxicity of cancer chemotherapeutic agents discusses several kinase inhibitors including imatinib, gefitinib, erlotinib and crizotinib, but not fostamatinib).
• Chabner BA, Barnes J, Neal J, Olson E, Mujagic H, Sequist L, Wilson W, et al. Targeted therapies: tyrosine kinase inhibitors, monoclonal antibodies, and cytokines. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 1731-54.

  (Textbook of pharmacology and therapeutics).
• https://www​.accessdata​.fda.gov/scripts/cder/daf/

  (FDA Drug Approvals website that has product labels [package inserts], letters of approval and full FDA scientific review of the new drug application for safety and efficacy).
• Spraggs CF, Xu CF, Hunt CM. Genetic characterization to improve interpretation and clinical management of hepatotoxicity caused by tyrosine kinase inhibitors. Pharmacogenomics 2013; 14: 541-54. [PubMed: 23556451]

  (Review of genetic associations of serum ALT and bilirubin elevations during therapy with tyrosine kinase inhibitors focusing on lapatinib and pazopanib; fostamatinib is not mentioned).
• Genovese MC, van der Heijde DM, Keystone EC, Spindler AJ, Benhamou C, Kavanaugh A, Fudman E, et al. A phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 2 dosing regimens of fostamatinib in patients with rheumatoid arthritis with an inadequate response to a tumor necrosis factor-α antagonist. J Rheumatol 2014; 41: 2120-8. [PubMed: 25225285]

  (Among 323 patients with rheumatoid arthritis on methotrexate enrolled in a randomized controlled trial for 24 weeks, clinical responses were more frequent with fostamatinib [36% and 28%] than placebo [21%], but so were side effects including diarrhea [20% and 27% vs 6%] and hypertension [13% and 14% vs 8%] and ALT elevations above 3 times ULN [4% and 2% vs 2%], and there were no liver related serious adverse events).
• Taylor PC, Genovese MC, Greenwood M, Ho M, Nasonov E, Oemar B, Stoilov R, et al. OSKIRA-4: a phase IIb randomised, placebo-controlled study of the efficacy and safety of fostamatinib monotherapy. Ann Rheum Dis 2015; 74: 2123-9. [PubMed: 25074688]

  (Among 279 patients with rheumatoid arthritis treated with fostamatinib or adalimumab or placebo for 6 weeks, clinical improvements were more frequent with fostamatinib than placebo as were adverse events, ALT elevations above 5 times ULN occurring in 4% vs 2% on placebo).
• Bussel J, Arnold DM, Grossbard E, Mayer J, Treliński J, Homenda W, Hellmann A, et al. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: results of two phase 3, randomized, placebo-controlled trials. Am J Hematol 2018; 93: 921-30. [PMC free article: PMC6055608] [PubMed: 29696684]

  (Among 150 patients enrolled in 2 controlled trials of a 24-week course of fostamatinib in patients with chronic immune thrombocytopenia, response in platelet counts were more frequent with fostamatinib vs placebo [43% vs 14%] as were adverse side effects including ALT elevations [11% vs 0%], but there were no cases of clinically apparent liver injury in either group).
• Newland A, Lee EJ, McDonald V, Bussel JB. Fostamatinib for persistent/chronic adult immune thrombocytopenia. Immunotherapy 2018; 10: 9-25. [PubMed: 28967793]

  (Review of the basis of use, clinical efficacy and safety of fostamatinib in therapy of immune thrombocytopenia mentions that ALT elevations above twice normal occur in up to 12% of patients, but are generally mild and transient and not accompanied by symptoms or jaundice).
• Markham A. Fostamatinib: first global approval. Drugs 2018; 78: 959-63. [PubMed: 29869203]

  (Review of the history of the development of fostamatinib, its mechanism of action, pharmacology, clinical efficacy and safety).